Purpose <p>The Limb Injury Measurement Battery for Quality of Life (LIMB-QOL) was developed to comprehensively assess patient reported outcomes (PRO) for research and clinical use with individuals who have sustained major extremity trauma and limb loss.</p> Methods <p>A mixed-methods approach was used that included qualitative focus groups with civilians, service members, and clinicians as well as quantitative PRO data collection with individuals with a history of major traumatic limb injury or limb-loss due to such trauma or sudden-onset illness. Individuals with dysvascular and other chronic disease causes were excluded. Qualitative data were collected via focus groups (<i>n</i> = 56 individuals with major extremity trauma; <i>n</i> = 34 clinicians) and cognitive debriefing interviews (<i>n</i> = 41 individuals with major extremity trauma). Quantitative data were obtained through structured phone interviews with a large sample representing the target limb trauma and limb loss population (<i>n</i> = 603). Newly developed item banks were calibrated using graded response model item response theory analysis.</p> Results <p>LIMB-QOL includes 25 measurement scales including 10 new, targeted item banks developed with and for individuals with major limb trauma and 15 existing PRO item banks measuring salient physical, emotional, and social aspects of health-related QOL. Computer adaptive tests and short forms were programmed into the Assessment Center application programming interface and are now available through REDCap and other platforms.</p> Conclusion <p>LIMB-QOL provides a comprehensive and standardized system of PRO assessments for individuals with amputation or limb preservation due to sudden-onset limb injury. Research and clinical applications are discussed.</p>